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- Assessment of the effectiveness of allergic rhinitis medications using a target trial emulation approach based on mobile health dataPublication . Amaral, Rita; Bousquet, Jean; Amaral, RitaRandomised controlled trials (RCTs) are the paradigm for questions on causal inference but often face challenges in generalisability due to strict eligibility criteria. In allergic rhinitis (AR), this limitation is particularly relevant, with RCTs on AR displaying an overrepresentation of patients with severe disease and not providing sufficiently detailed information on the impact of comorbidities on treatment effectiveness. Mobile health (mHealth) applications provide an opportunity to collect large-scale patient-reported data that can complement traditional trial evidence and broaden our understanding of treatment effectiveness in routine care. However, to adequately use mHealth data for that purpose, approaches to adequately deal with confounding must be applied.
- Meningeal γδ T cells facilitate bacterial entry into the brain in neonatal meningitis and trigger long-term behavioural sequelaePublication . Lorga, Inês; Soares, Joana; Bravo, Joana; Mesquita, Pedro; Ribeiro, Nuno; Rodrigues, João; Hassan, Ahmed; Mesquita, Morgana; Cavadas, Bruno; Georgiev, Hristo; Magalhães, Ana; Summavielle, Teresa; Vilanova, Manuel; Ribot, Julie C.; Andrade, Elva Bonifácio; Bonifácio Andrade, Elva; Summavielle, TeresaNeonatal bacterial meningitis is a life-threatening condition and a leading cause of neurodevelopmental impairment among survivors. Despite its prevalence, the role of meningeal immunity on disease pathology during early life remains largely unexplored. Using a clinically relevant mouse model of neonatal group B streptococcal meningitis and single-cell RNA sequencing, we observed that IL-17A (IL-17)-producing γδ T cells (γδ17 T cells) accumulate in the meninges during the acute phase of infection and persist throughout the lifespan. Importantly, mice deficient in γδ T cells or in IL-17 show a significantly lower bacterial colonisation in the brain parenchyma, and IL-17 neutralisation in the cerebrospinal fluid leads to a similar phenotype. Reduced blood-brain barrier permeability in the absence of γδ T cells results in decreased bacterial invasion and diminished microglia activation. Wild-type but not γδ T cell-deficient mice surviving infection exhibit increased hyperactivity and open space anxiety during early adulthood, a behavioural profile that may reflect attention deficit and hyperactivity (ADHD)-like tendencies. Altogether, these findings establish a pathogenic role for meningeal γδ17 T cells in early life, uncovering a key mechanism that drives long-term sequelae in GBS neonatal meningitis.